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Reduced intensity versus non-myeloablative conditioning regimen for haploidentical transplantation and post-transplantation cyclophosphamide in complete remission acute myeloid leukemia: a study from the ALWP of the EBMT

Bone Marrow Transplantation volume 57, pages 1421–1427 (2022)Cite this article

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Abstract

The optimal conditioning regimen prior haploidentical stem cell transplantation (Haplo-SCT) with post transplantation cyclophosphamide (PT-Cy) for acute myeloid leukemia (AML) remains unknown. A non-myeloablative conditioning (NMAC) regimen (cyclophosphamide + fludarabine + TBI 2 Gy [CyFluTBI]) is a safe approach, but relapse incidence remains high in this setting. Alternatively, a reduced intensity conditioning (RIC) regimen combining thiotepa and reduced-dose busulfan with fludarabine (TBF) may decrease AML relapse. However, an excess of toxicity may counterbalance this potential benefit. We retrospectively compared CyFluTBI vs. TBF in CR AML patients who underwent Haplo-SCT with PT-Cy, in two different populations based on age. We analyzed 490 patients. In patients aged <60 years (n = 203), we observed a higher RI (HR = 3.59, 95% CI = 1.75–7.37, p < 0.01), lower LFS (HR = 1.98, 95% CI = 1.22–3.22, p < 0.01) and lower OS (HR = 1.73, 95% CI = 1.04–2.88, p = 0.04) in the CyFluTBI group, without significant difference in NRM. In older patients (n = 287), we observed that conditioning regimen did not significantly influence LFS (HR = 0.90, 95% CI = 0.56–1.44, p = 0.65), OS (HR = 0.81, 95% CI = 0.49–1.32, p = 0.39) and RI (HR = 1.78, 95% CI = 0.90–3.50, p = 0.10), but showed that CyFluTBI was associated with a significantly lower risk of NRM (HR = 0.48, 95% CI = 0.25–0.92, p = 0.03). Thus, younger patients seem to benefit from conditioning intensification from CyFluTBI to TBF regimens prior PT-Cy Haplo-SCT for CR AML, while older ones do not.

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Fig. 1: Outcome after Haplo-SCT in patients aged <60 years according to conditioning regimen.
Fig. 2: Outcome after Haplo-SCT in patients aged ≥60 years according to conditioning regimen.

Data availability

Data is available on a specific request to the ALWP of EBMT.

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Acknowledgements

We thank Emmanuelle Polge and Irma Khvedelidze from the EBMT Paris Study Unit. The list of participating centers is provided in the Supplementary Appendix 1.

Author information

Authors and Affiliations

  1. Hematology and Transplantation, Institut Paoli-Calmettes, Aix Marseille Univ, CNRS, INSERM, CRCM, Marseille, France

    Raynier Devillier & Didier Blaise

  2. EBMT Statistical Unit, Paris, France

    Jacques-Emmanuel Galimard & Myriam Labopin

  3. Hematology and Transplant Center, IRCCS Ospedale Policlinico San Martino, Genova, Italy

    Anna Maria Raiola

  4. Centre for Haematology, Imperial College London, Hammersmith Hospital, London, UK

    Jiri Pavlu

  5. Transplantation Unit, Department of Oncology and Hematology, Instituto Clinico Humanitas, Milano, Italy

    Luca Castagna

  6. Hôpital St. Louis, Dept.of Hematology – BMT, Paris, France

    Gerard Socié

  7. Département d’Oncologie, Service d’Hématologie, Hôpitaux Universitaires De Genève and Faculty of Medicine, University of Geneva, Geneva, Switzerland

    Yves Chalandon

  8. Grande Ospedale Metropolitano Bianchi Melacrino Morelli - Centro Unico Trapianti Alberto Neri - Reggio Calabria, Calabria, Italy

    Massimo Martino

  9. University Hospital Dresden Medizinische Klinik und Poliklinik I, TU Dresden, Germany

    Friedrich Stölzel

  10. Goethe-Universitaet, Medizinische Klinik II, Hämatologie, Medizinische Onkologie, Frankfurt, Germany

    Gesine Bug

  11. S.S.C.V.D Trapianto di Cellule Staminali, A.O.U Citta della Salute e della Scienza di Torino, Torino, Italy

    Benedetto Bruno

  12. University Hospital Centre Zagreb, Zagreb, Croatia

    Radovan Vrhovac

  13. University of Amiens: CHU Amiens, Service d’Hematologie, Amiens, France

    Amandine Charbonnier

  14. Azienda Ospedali Riuniti di Ancona, Department of Hematology, Ancona University, Ancona, Italy

    Attilio Olivieri

  15. CHU ESTAING, Service d’hématologie, Clinique Adulte, Clermont-Ferrand, France

    Jacques-Olivier Bay

  16. Department of Hematology, Hosp. Reina Sofia, Córdoba Hospital, Córdoba, Spain

    Herrera Arroyo

  17. CHU de Lille, LIRIC, INSERM U995, Université de Lille, Lille, France

    Ibrahim Yakoub-Agha

  18. Kings College Hospital, Dept. of Haematological Medicine, Denmark Hill, London, UK

    Daniele Avenoso

  19. Philipps Universitaet Marburg, University Hospital Giessen and Marburg, Campus Marburg, Baldingerstr., Marburg, Germany

    Andreas Neubauer

  20. Universite Paris IV, Hopital la Pitié-Salpêtrière, Hematologie Clinique, Paris, France

    Stéphanie Nguyen

  21. CHU Bordeaux, Hôpital Haut-L’évêque, - Pessac, Bordeaux, France

    Edouard Forcade

  22. Hematology, Saint Antoine University Hospital, Paris, France

    Eolia Brissot & Mohamad Mohty

  23. Division of Hematology and Medical Oncology, Vanderbilt University Medical Center, Nashville, TN, USA

    Bipin Savani

  24. Hematology Division, Chaim Sheba Medical Center, Tel-Hashomer, Israel

    Arnon Nagler

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  1. Raynier Devillier
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  2. Jacques-Emmanuel Galimard
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Contributions

RD designed the study. RD, JEG and MM interpreted the data, and wrote the manuscript draft and final version. JEG and ML performed the statistical analysis. RD, DB, AMR, JP, LC, GS, YC, MM, FS, GB, BB, RV, AC, AO, JOB, HA, IYA, DA, AN, SN, EF, EB, BS, AN, and MM provided patient data. All authors contributed to the manuscript and critically reviewed the final version.

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Correspondence to Raynier Devillier.

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Devillier, R., Galimard, JE., Labopin, M. et al. Reduced intensity versus non-myeloablative conditioning regimen for haploidentical transplantation and post-transplantation cyclophosphamide in complete remission acute myeloid leukemia: a study from the ALWP of the EBMT. Bone Marrow Transplant 57, 1421–1427 (2022). https://doi.org/10.1038/s41409-022-01674-x

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